Human-animal chimeras: Stanford scientists condemn funding ban

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Stanford University stem cell biologist Sean Wu, who studies the early development of heart cells, says a new federal funding ban on "chimera" research could slow his future study of growing human tissue in animals to help people with failing hearts.

STANFORD — The Obama administration has quietly clamped a moratorium on a new type of stem-cell research, triggering a letter from a group of Stanford scientists condemning the move and saying that it could delay discoveries in a promising field of medicine.

The research — which strives to grow human organs in animals, called “chimeras,” after the hybrid creatures in Greek mythology — could lead to an endless supply of organs for transplantation and improved drug testing, proponents say. But it also poses ethical and animal welfare concerns.

The abrupt suspension of federal funding for this research “impedes scientific progress in regenerative medicine and should be lifted,” said a letter from the Stanford scientists published Thursday in the journal Science.

In a startling reversal of policy, reminiscent of the Bush administration’s 2001 ban on embryonic stem cell funding, the federal government issued a notice Sept. 23 saying it would stop funding chimera research while it deliberates future policy.

NIH officials did not immediately respond to the criticism, but in a September statement, they vigorously defended the need to hit the pause button.

The suspension offers “a unique opportunity to take a deep breath … and consider whether any additional policies are needed to promote the responsible conduct of this promising science,” said Carrie D. Wolinetz, associate director for Science Policy at the National Institutes of Health.

On Friday, Stanford experts such as the School of Medicine’s Hiromitsu Nakauchi and the law school’s Hank Greely will testify at NIH’s headquarters in Bethesda, Maryland, about the science and funding restrictions, as the agency deliberates its next step.

Without federal funding, California-based researchers would look to the California Institute of Regenerative Medicine for support. The institute, created by passage of Proposition 71 in 2004, was designed to circumvent federal restrictions on embryonic stem cell research. But NIH has a much bigger pot of money for biomedical research.

The federal funding ban could influence the scope of work by Stanford’s Nakauchi, who has pioneered an approach that may allow stem cells from a patient to become the seeds for new, genetically matched organs that are grown in large animals. With researchers at UC Davis, he is planning to inject human stem cells into sheep embryos.

His work is now funded by the California Institute for Regenerative Medicine, but he had planned to apply to NIH to expand the work.

This approach could create a huge supply of livers, lungs and other organs for transplantation, scientists say. It could also solve the problem of rejected organs, because they would match the patients’ immune systems.

In addition, human-animal chimeras could serve as new models for discovering and testing drugs.

“I do think such research can be conducted responsibly,” Greely said, “but I’m especially interested in hearing exactly what research is concerning NIH — and why NIH is concerned.”

Stem-cell-based research into chimeras has been underway at Stanford for years, Greely said, noting that safety and ethics of the work has been overseen by the state’s Stem Cell Research Oversight Committee.

Weissman has no plans to build a mouse with a human brain but seeks to create a way to learn more about devastating brain diseases such as stroke, schizophrenia, Alzheimer’s and Lou Gehrig’s disease — impairments not easily studied in people.

Critics assert that animals should not be injected with human neural stem cells because it might confer human cognitive, psychological and emotional traits. They also warn against creating animals with human cells that could breed or escape from the laboratory.

The National Academy of Medicine and the National Research Council have long argued against breeding animals with human pluripotent stem cells — adult cells that have been genetically reprogrammed to become embryonic stem cells — implanted into embryos, to prevent any possible transmission of human genes via the sperm or egg of the animal. They also urged banning the use of monkeys and other primates, which are considered too similar to humans, for such studies.

But recent “breakthrough leaps” in technology means now is the time to put more formal policies in place, according to the statement by NIH’s Wolinetz.

“Simply put, the wheels of science often turn faster than the wheels of policy,” she said.

Stem cell science has progressed so quickly that tissue engineering now seems within reach, scientists say.

“The science is maturing to a stage where people can do more targeted and more specific research to grow an organ,” said Geoffrey Lomax of the California Institute of Regenerative Medicine. “They understand the whole cycle — from stem cells to the blood system and the organ system.”

But it is very difficult to grow an organ in a petri dish, in part because the process involves complex biochemical signaling that only a body provides. So scientists envision using animals as incubators.

“Currently, it is impossible to accurately recapitulate human development,” according to the seven Stanford biologists writing in Science. The letter also was co-authored by four prominent scientists from other research institutions across the country.

Stanford’s Sean Wu, who received an NIH award to study interspecies chimeras, said he was startled and distressed by the news.

He dreams of the day that work in cardiac stem cells in mice “might be able to create organs for human transplant, using stem cells from individuals who are missing or have defective organ function,” he said.

A ban on NIH support would have a chilling effect on many other future discoveries, Wu said.

“If young investigators hear there is no federal funding,” he said, “why would they start a career in the field?”

The seven Stanford scientists who urge lifting of National Institutes of Health restrictions on chimera research are:

Arun Sharma, of the Institute of Stem Cell Biology and Regenerative Medicine and Cardiovascular Institute.Vittorio Sebastiano, of the Institute of Stem Cell Biology and Regenerative Medicine and Department of Obstetrics and Gynecology.Christopher Scott and David Magnus, both of the Center for Biomedical Ethics.Hiromitsu Nakauchi, of the Institute of Stem Cell Biology and Regenerative Medicine and Department of Genetics.Joseph Wu, of the Institute of Stem Cell Biology and Regenerative Medicine and Cardiovascular Institute.Irving Weissman, of the Institute for Stem Cell Biology and Regenerative Medicine and Department of Pathology.Sean Wu, of the Institute of Stem Cell Biology and Regenerative Medicine and Cardiovascular Institute.Four non-Stanford scientists also signed the letter.

Lisa M. Krieger is a science writer at The Mercury News, covering research, scientific policy and environmental news from Stanford University, the University of California, NASA-Ames, U.S. Geological Survey and other Bay Area-based research facilities. Lisa also contributes to the Videography team. She graduated from Duke University with a degree in biology. Outside of work, she enjoys photography, backpacking, swimming and bird-watching.